Topical N-acetyl-S-farnesyl-L-cysteine inhibits mouse skin inflammation, and unlike dexamethasone, its effects are restricted to the application site

Joel S. Gordon, Peter M. Wolanin, Arnold V. Gonzalez, David A. Fela, Gopal Sarngadharan, Karl Rouzard, Eduardo Perez, Jeffry B. Stock, Maxwell B. Stock

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

N-Acetyl-S-farnesyl-L-cysteine (AFC), a modulator of G protein and G-protein coupled receptor signaling, inhibits neutrophil chemotaxis and other inflammatory responses in cell-based assays. Here, we show topical AFC inhibits in vivo acute inflammation induced by 12-O-tetradecanoyl-phorbol-13-acetate (TPA) and arachidonic acid using the mouse ear model of inflammation. AFC inhibits edema, as measured by ear weight, and also inhibits neutrophil infiltration as assayed by direct counting in histological sections and by measuring myeloperoxidase (MPO) activity as a neutrophil marker. In addition, AFC inhibits in vivo allergic contact dermatitis in a mouse model utilizing sensitization followed by a subsequent challenge with 2,4-dinitrofluorobenzene. Unlike the established anti-inflammatories dexamethasone and indomethacin, AFC's action was restricted to the site of application. In this mouse model, both dexamethasone and indomethacin inhibited TPA-induced edema and MPO activity in the vehicle-treated, contralateral ear. AFC showed no contralateral ear inhibition for either of these end points. A marginally significant decrease due to AFC treatment was seen in TPA-induced epidermal hyperplasia at 24 hours. This was much less than the 90% inhibition of neutrophil infiltration, suggesting that AFC does not act by directly inhibiting protein kinase C.

Original languageEnglish (US)
Pages (from-to)643-654
Number of pages12
JournalJournal of Investigative Dermatology
Volume128
Issue number3
DOIs
StatePublished - Mar 2008

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

Fingerprint Dive into the research topics of 'Topical N-acetyl-S-farnesyl-L-cysteine inhibits mouse skin inflammation, and unlike dexamethasone, its effects are restricted to the application site'. Together they form a unique fingerprint.

  • Cite this